Vascular inducing implants

ABSTRACT

Implants and associated delivery systems for promoting angiogenesis in ischemic tissue are provided. The implants may be delivered percutaneously, thoracically or surgically and are particularly well suited for implantation into the myocardium of the heart. The implants are configured to have a first configuration having a low profile and an expanded, second configuration having a large profile. The implants are delivered to the ischemic tissue location in the first configuration, implanted then expanded to the second configuration. The expanded implants maintain a stress on the surrounding tissue, irritating and slightly injuring the tissue to provoke an injury response that results in angiogenesis. The flow of blood from the surrounding tissue into the implant and pooling of the blood in and around the implant leads to thrombosis and fibrin growth. This healing process leads to angiogenesis in the tissue surrounding the implant. Additionally, the implants may contain an angiogenic substance or a thrombus of blood, preloaded or injected after implantation to aid in initiating angiogenesis.

RELATED APPLICATION

This application is a divisional of application Ser. No. 09/774,319filed Jan. 31, 2001, now U.S. Pat. No. 6,709,425, which is a divisionalof application Ser. No. 09/164,173 filed Sep. 30, 1998, now U.S. Pat.No. 6,458,092.

FIELD OF THE INVENTION

This invention relates to methods and devices for inducing angiogenesisin ischemic tissue.

BACKGROUND OF THE INVENTION

Tissue becomes ischemic when it is deprived of oxygenated blood. Bloodmay be present in such tissue, though it is not carrying oxygen.Ischemic tissue can be revived to function normally if it has remainedviable despite the deprivation of oxygenated blood. Ischemia can becaused by a blockage in the vascular system that prohibits oxygenatedblood from reaching the affected tissue area. Ischemia causes pain inthe area of the affected tissue and in the case of muscle tissue caninterrupt muscular function.

Although ischemia can occur in various regions of the body, often tissueof the heart, the myocardium, is affected by ischemia due to coronaryartery disease, occlusion of the coronary artery, which otherwiseprovides blood to the myocardium. Muscle tissue affected by ischemia cancause pain to the individual affected. Ischemia can be treated, if atissue has remained viable despite the deprivation of oxygenated blood,by restoring blood flow to the affected tissue.

Treatment of myocardial ischemia has been addressed by severaltechniques designed to restore blood supply to the affected region.Coronary artery bypass grafting CABG involves grating a venous segmentbetween the aorta and the coronary artery to bypass the occluded portionof the artery. Once blood flow is redirected to the portion of thecoronary artery beyond the occlusion, the supply of oxygenated blood isrestored to the area of ischemic tissue.

Early researchers, more than thirty years ago, reported promisingresults for revascularizing the myocardium by piercing the muscle tocreate multiple channels for blood flow. Sen, P. K. et al.,“Transmyocardial Acupuncture—A New Approach to MyocardialRevascularization”, Journal of Thoracic and Cardiovascular Surgery, Vol.50, No. 2, August 1965, pp. 181-189. Although others have reportedvarying degrees of success with various methods of piercing themyocardium to restore blood flow to the muscle, many have faced commonproblems such as closure of the created channels. Various techniques ofperforating the muscle tissue to avoid closure have been reported byresearchers. These techniques include piercing with a solid sharp tipwire, hypodermic tube and physically stretching the channel after itsformation. Reportedly, many of these methods still produced trauma andtearing of the tissue that ultimately led to closure of the channel.

An alternative method of creating channels that potentially avoids theproblem of closure involves the use of laser technology. Researchershave reported success in maintaining patent channels in the myocardiumby forming the channels with the heat energy of a laser. Mirhoseini, M.et al., “Revascularization of the Heart by Laser”, Journal ofMicrosurgery, Vol. 2, No. 4, June 1981, pp. 253-260. The laser was saidto form channels in the tissue that were clean and made without tearingand trauma, suggesting that scarring does not occur and the channels areless likely to experience the closure that results from healing. AitaU.S. Pat. Nos. 5,380,316 and 5,389,096 disclose another approach to acatheter based laser system for TMR.

Although there has been some published recognition of the desirabilityof performing transmyocardial revascularization (TMR) in a non-lasercatheterization procedure, there does not appear to be evidence thatsuch procedures have been put into practice. For example, U.S. Pat. No.5,429,144 Wilk discloses inserting an expandable stent within apreformed channel created within the myocardium for the purposes ofcreating blood flow into the tissue from the left ventricle

Performing TMR by placing stents in the myocardium is also disclosed inU.S. Pat. No. 5,810,836 (Hussein et al.). The Hussein patent disclosesseveral stent embodiments that are delivered through the epicardium ofthe heart, into the myocardium and positioned to be open to the leftventricle. The stents are intended to maintain an open a channel in themyocardium through which blood enters from the ventricle and perfusesinto the myocardium.

Angiogenesis, the growth of new blood vessels in tissue, has been thesubject of increased study in recent years. Such blood vessel growth toprovide new supplies of oxygenated blood to a region of tissue has thepotential to remedy a variety of tissue and muscular ailments,particularly ischemia. Primarily, study has focused on perfectingangiogenic factors such as human growth factors produced from geneticengineering techniques. It has been reported that injection of such agrowth factor into myocardial tissue initiates angiogenesis at thatsite, which is exhibited by a new dense capillary network within thetissue. Schumacher et al., “Induction of Neo-Angiogenesis in IschemicMyocardium by Human Growth Factors”, Circulation, 1998; 97:645-650. Theauthors noted that such treatment could be an approach to management ofdiffused coronary heart disease after alternative methods ofadministration have been developed.

SUMMARY OF THE INVENTION

The vascular inducing implants of the present invention provide amechanism for initiating angiogenesis within ischemic tissue. Theimplants interact with the surrounding tissue in which they areimplanted and the blood that is present in the tissue to initiateangiogenesis by various mechanisms.

Primarily, it is expected that the implants will trigger angiogenesis inthe ischemic tissue by interacting in one or more ways with the tissueto initiate an injury response. The body's response to tissue injuryinvolves thrombosis formation at the site of the injury or irritation.Thrombosis leads to arterioles and fibrin growth which is believed toultimately lead to new blood vessel growth to feed the new tissue withblood. The new blood vessels that develop in this region also serve tosupply blood to the surrounding area of ischemic tissue that waspreviously deprived of oxygenated blood.

The implant devices may be formed in a variety of configurations tocarry out the objectives outlined above for initiating angiogenesis.Specifically, the implants can be arranged in various ways to provide afirst configuration that presents a reduced profile and a secondconfiguration that is expanded to provide a larger profile that willirritate and place stress on the surrounding tissue into which it hasbeen implanted. The first configuration is suitable for delivery to thetissue site and into the tissue. The second configuration is obtainedafter the implant is placed in the tissue. Expansion of the device tothe larger profile configuration not only places stress on the tissuebut serves to rupture and injure the tissue slightly as it expands. Thechange in profile between the first configuration and secondconfiguration is of such a magnitude that the irritation and injurysuffered by surrounding tissue upon expansion of the implant will inducean injury response that results in angiogenesis. However, the magnitudeof the expansion to the second configuration is not so great that tissuebecomes severely injured: function impaired and unable to heal.

Additionally, each implant embodiment serves to provide a constantsource of irritation and injury to the tissue in which it is implanted,thereby initiating the healing process in that tissue that is believedto lead to angiogenesis. As tissue surrounding the implant moves, suchas the contraction and relaxation of muscle tissue, some friction andabrasion from the implant occurs, which injures the tissue. The injurycaused by the outside surfaces of the implants to the surrounding tissuedoes not substantially destroy the tissue, but is sufficient to initiatean injury response and healing which leads to angiogenesis.

Implant embodiments of the invention also serve to initiate angiogenesisby providing an interior chamber into which blood may enter, collect andthrombose. Blood that enters the implant and remains, even temporarily,tends to coagulate and thrombus. Over time, continued pooling of theblood in the interior will cause thrombosis and fibrin growth throughoutthe interior of the implant and into the surrounding tissue. New bloodvessels will grow to serve the new growth with oxygenated blood, theprocess of angiogenesis.

Implant embodiments may further be prepared to initiate angiogenesis byhaving a thrombus of blood associated with them at the time of theirimplantation or inserted in the interior immediately followingimplantation. The thrombus of blood may be taken from the patient priorto the implant procedure and is believed to help initiate the tissue'shealing response which leads to angiogenesis.

Alternatively or in addition to a thrombus of blood, the implant devicesmay be associated with an angiogenic substance in a variety of ways toaid the process of angiogenesis, In embodiments having a definedinterior, the substance may be placed within the interior prior toimplantation or injected after the implantation of the device. Thesubstance may be fluid or solid. The blood flow into and interactingwith the interior of the device will serve to distribute the substancethrough the surrounding tissue area because blood entering the devicemixes with and then carries away the substance as it leaves the device.Viscosity of the substance and opening size through which it passes,determine the time-release rate of the substance.

Substances may be associated with the device, not only by being carriedwithin their interiors, but also by application of a coating to thedevice. Alternatively, the substance may be dispersed in the compositionof the device material. Alternatively, the implant may be fabricatedentirely of the angiogenic substance. Recognizing that there are manyways to attach an angiogenic substance or drug to a device, the methodslisted above are provided merely as examples and are not intended tolimit the scope of the invention. Regardless of the method ofassociation, the implants of the present operation operate to distributethe angiogenic substance in surrounding tissue by the implants contactwith the tissue and blood supply in that tissue area.

By way of example, the implant device may comprise a helical springhaving a first configuration that is more tightly wound, having anelongated length, more coils and a reduced diameter The secondconfiguration of the spring will provide an increased profile byincreasing the diameter of the coils through shortening the length ofthe spring.

In another embodiment, the implant may comprise a mesh tube comprised ofindividual wire-like elements that are woven and arranged to allow thetube to have a first configuration that is elongated with a smallerdiameter and a second configuration that is shortened in length, butcorrespondingly larger in diameter and profile. In yet anotherconfiguration, the implant may comprise a sheet of solid or porousmaterial that is rolled into a tube. A first, reduced profileconfiguration of the tube is tightly rolled upon itself, storingpotential energy that will provide resilient expansion of the rolledtube to a less tightly rolled tubular shape when released. The expandedconfiguration of the tube provides a second configuration of the implantthat has a larger profile. In another embodiment, the implant maycomprise a spine having spaced along its length several C-shaped ringsthat may be compressed into a smaller profile in which the rings areclosed and a second configuration having an increased profile whereinthe rings are opened to a C-shape. The ends of the C-shaped rings may beformed to have eyelets that meet and are concentrically arranged whenthe rings are closed so that a release pin can be inserted through themto hold them in their reduced profile configuration. Once the implant isplaced within the tissue, the release pin may be removed permitting therings to resiliently expand to a C configuration.

In another embodiment, the implant may have a first configuration thatis uniaxial and a second configuration that is biaxial or bifurcated toprovide an increased profile. The bifurcated embodiments disclosed maybe comprised of single or double helical coils arranged to have a trunkportion and two leg portions. The resulting appearance is similar to apair of pants. Alternatively, the bifurcated embodiment may beconfigured as two spines having loops mounted concentrically along theirlength, the spines being joined to several common loops at one end toform a trunk portion, and the other ends of the spine being free to formthe leg portions of the implant. In both bifurcated implant embodiments,the loops or coils are interleaved while maintained in the firstconfiguration such that they lie substantially along the same axis. Inthe second configuration, the spines spring apart to form a Y-shaped orbifurcated configuration presenting a larger profile to increase theinjury to surrounding tissue and initiate angiogenesis.

Alternatively, the device may comprise a body that has attached theretoflexible elements configured to retain, at least temporarily, blood orangiogenic substances. An example of such an embodiment would be a smallbrush having an axial core member with a plurality of flexible bristlesextending radially therefrom. The bristles having a natural resilienceto a radially outward configuration with respect to the core. Duringdelivery of the brush into tissue, the bristles are swept back againstthe core. However, after insertion, the resilient bristles return atleast partially to their radially outward extending configuration,thereby placing surrounding tissue in stress and causing irritation tothe tissue. The bristles are also configured to absorb, or hold within ahollow interior a drug or amount of quantity of blood. Additionally, thecore member may be configured to define a hollow interior capable ofholding a therapeutic substance.

One or more implants of the present invention may be applied to an areaof ischemic tissue. By way of example, the implants may define a widthof approximately 2 mm and a length corresponding to somewhat less thanthe thickness of the tissue into which it is implanted. It isanticipated that implants having a 2 mm wide profile would serve an areaof ischemic tissue of approximately one square centimeter to adequatelypromote angiogenesis throughout the surrounding region of tissue yetavoid altering the movement of the tissue due to a high density offoreign objects within a confined region of tissue.

The implants are delivered directly into the subject tissue withoutpreforming a channel by removal of tissue such as by coring or ablationby a laser. The delivery devices, while loaded with the implant, operateto pierce and penetrate the tissue in a single driving motion. While thedelivery device is penetrating the tissue, the implant is released andexpanded into its second configuration within the tissue. The expandedimplant is left behind as the delivery device is withdrawn. Uponexpansion of the device, the surrounding tissue may tear and becomeinjured as it is pushed aside by the implant. The stressed tissue alsotries to recoil around the device and may herniate through openings inthe structure of the device. It is not important that the implantmaintain an open channel through the tissue for blood to flow. Theobjective of the implant is to trigger angiogenesis, so that new bloodvessels will be created to introduce blood flow to the region.

The devices may be implanted percutaneously and transluminally,thoracically or surgically by a cut down method. In the case of implantsplaced within myocardial tissue of the heart, delivery systems aredisclosed for percutaneously accessing the left ventricle of the heartand penetrating and delivering the implant into the myocardium.

It is an object of the present invention to provide a method ofpromoting angiogenesis within ischemic tissue.

It is another object of the present invention to provide a method ofpromoting angiogenesis by implanting a device within ischemic tissue.

It is another object of the present invention to provide a method ofpromoting angiogenesis by causing thrombosis in the area of ischemictissue.

It is another object of the present invention to provide a process ofpromoting angiogenesis within ischemic myocardial tissue of the heart.

It is another object of the invention to provide an implant suitable forimplantation within tissue of the human body.

It is another objective of the present invention to provide an implantdelivery system that is safe and simple to use while minimizing traumato the patient.

It is another object of the invention to provide an implant that willirritate tissue that surrounds the implant to initiate a healingresponse that leads to angiogenesis.

It is another object of the invention to provide an implant having asmall profile first configuration and large profile second configurationafter implantation into tissue such that the implant places stress onthe surrounding tissue.

It is another object of the invention to provide an implant that isconfigured to have associated with it an angiogenic substance thatpromotes angiogenesis within tissue surrounding the implant.

It is another object of the invention to provide an implant configuredto interact with blood present in the tissue into which the implant isinserted.

It is another object of the invention to provide an implant that definesan interior into which blood can enter and thrombose.

It is another object of the invention to provide an implant to which athrombus of blood or an angiogenic substance can be inserted before orafter the implant has been inserted into tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects and advantages of the invention will beappreciated more fully from the following further description thereof,with reference to the accompanying diagrammatic drawings wherein:

FIG. 1A shows a side view of a spring implant embodiment in its smallprofile, first configuration;

FIG. 1B shows a side view of a spring implant embodiment in its largeprofile second configuration;

FIG. 1C shows an alternate spring implant embodiment in its smallprofile first configuration;

FIG. 1D shows an alternate spring implant embodiment in its largeprofile second configuration;

FIG. 2A is a side view of the spring implant embodiment in its lowprofile, first configuration being delivered to a tissue location;

FIG. 2B is a diagrammatical sectional illustration of the implantexpanded to its second configuration within a tissue location;

FIG. 2C shows a side view of the alternate spring embodiment mounted ona delivery device;

FIG. 3 shows a sectional illustration of the left ventricle of a humanheart having several implants of the present invention;

FIGS. 4A-4D show a sectional illustration of the left ventricle of ahuman heart with a steerable delivery catheter positioned within theventricle to deliver implants into the myocardium, and FIG. 4E shows alongitudinal cross-sectional view of a steerable delivery catheter;

FIG. 5A shows a side view of a mesh tube implant in its low profilefirst configuration;

FIG. 5B shows a side view of a mesh tube implant in its large profilesecond configuration;

FIG. 5C shows a detailed view of the band of the mesh tube embodiment;

FIG. 6A shows a side view of the mesh tube embodiment in its low profilefirst configuration being delivered into a tissue location;

FIG. 6B shows a sectional illustration of the mesh tube implant itslarge profile, second configuration residing within tissue;

FIG. 7A shows a perspective view of a rolled tube implant in its smallprofile first configuration;

FIG. 7B shows a perspective view of the rolled tube implant in its largeprofile second configuration;

FIG. 8A is a side view of a sheet of material used to form the rolledtube implant;

FIG. 8B shows an end view of a sheet of material used to form the rolledtube implant;

FIG. 9A is a side view and partial cut-away view of the rolled tubeimplant being delivered to a tissue location through a delivery device;

FIG. 9B is a cross-sectional view taken along the line 9A-9B of FIG. 9A;

FIG. 9C is a side view illustration of the rolled tube implant placedwithin tissue and expanded into its second configuration;

FIG. 9D is a cross-sectional view of the rolled tube implant viewedalong the line 9D in FIG. 9C;

FIG. 10A is a perspective view of an implant comprising a spine andplurality of rings in its small profile first configuration;

FIG. 10B is a perspective view of the implant comprised of a spine andplurality of rings in its large profile second configuration;

FIG. 11A is a side view of the implant comprised of a spine andplurality of rings in its low profile, first configuration beingdelivered to a tissue location;

FIG. 11B is a cross-sectional view of the implant comprised of a spineand a plurality of rings viewed along the line 11B—11B in FIG.11A;

FIG. 11C is a section side view of the implant comprised of a spine andplurality of rings in its large profile, second configuration placedwithin tissue;

FIG. 11D is a cross-sectional view of the implant comprised of a spineand a plurality of rings viewed along the line 11D—11D in FIG. 11C;

FIG. 12A is a side view of a bifurcated implant in its low profile firstconfiguration;

FIG. 12B is a front view of a bifurcated implant in its low profilefirst configuration;

FIG. 12C is a side view of a bifurcated implant in its large profilesecond configuration;

FIG. 12D is a front view of a bifurcated implant in its large profilesecond configuration;

FIG. 13 is a side view of an alternate bifurcated implant having aslanted piercing edge in its low profile first configuration;

FIG. 14A is a side view of a bifurcated implant in its low profile firstconfiguration being delivered to a tissue location;

FIG. 14B is a sectional side view of a bifurcated implant in its largeprofile, second configuration placed within tissue;

FIG. 15A is a top view of a bifurcated open spring implant in its lowprofile first configuration;

FIG. 15B is a top view of a open spring bifurcated implant in its largeprofile second configuration;

FIG. 15C is a side view of an open spring bifurcated implant in its lowprofile first configuration;

FIG. 15D is a side view of an open spring bifurcated implant in itslarge profile second configuration;

FIG. 16A is a side view of an open spring bifurcated implant beingdelivered to a tissue location;

FIG. 16B is a sectional side view of an open spring bifurcated implantlocated within tissue and expanded to its large profile secondconfiguration;

FIG. 17A is a top view of a bifurcated spine and hoop implant in its lowprofile first configuration;

FIG. 17B is a top view of a bifurcated spine and hoop implant in itslarge profile second configuration;

FIG. 17C is a side view of a bifurcated spine and hoop implant in itslow profile first configuration;

FIG. 17D is a side view of a bifurcated spine and hoop implant in itslarge profile second configuration;

FIG. 18A is a side view of a bifurcated spine and hoop implant in itslow profile, first configuration being delivered to a tissue location;

FIG. 18B is a sectional side view of a bifurcated spine and hoop implantplaced within tissue and expanded to its large profile secondconfiguration;

FIG. 19A is a side view of a flexible brush implant.

FIG. 19B is an end view of the flexible brush implant.

FIG. 19C is a side view of the flexible brush implant at its postdelivery configuration.

FIG. 19D is a side view of a flexible brush implant having a core formedof twisted wires;

FIG. 19E is a section view of the flexible brush implant show in FIG.19D;

FIG. 19F is a partial cut-away view of the flexible brush implant andassociated delivery system penetrating the intended tissue location;

FIG. 19G is a partial cut-away view of an implanted flexible brushimplant and its associated delivery system being withdrawn.

DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENT

FIGS. 1A and 1B show a first embodiment of the implant comprising ahelical coil spring 10. The spring is formed from a filament 12 offlexible material such as stainless steel or other metal or high densitypolymer. The filament is helically wrapped to form several individualcoils 14 that comprise a spring having an interior 15. At each end 16 ofthe spring, the filament 12 terminates with a small tab 18 extending ina plane parallel to the axis of the implant. The tabs 18 are used formaintaining the implant upon the delivery device as will be described infurther detail below. FIGS. 1C and 1D show an alternative spring implantembodiment 26 comprised of two segments 27 that are wound in oppositedirections and joined together by a bridge 29. Each segment has a freeend in which the filament 12 terminates in a bulbous tab 18.

The spring implant embodiments are easily arranged from a firstconfiguration to a second configuration, where the second configurationof the implant has a larger profile than that presented while in thefirst configuration. Profile may be defined as the maximum width, or inthe case of a coil, the diameter, of the device. FIGS. 1A and 1C showthe device in a small profile, first configuration that is suitable fordelivery of the device into the tissue. FIGS. 1B and 1C show the implantdevices in a larger profile, second configuration into which the implantis transformed after delivery to place surrounding tissue in stress.

In its first configuration, shown in FIGS. 1A and 1C, the spring iswrapped more tightly, having a longer length L₁ and more coils 14 andthus a smaller diameter D₁ than in the second configuration shown inFIGS. 1B and 1D. In the second configuration, shown in FIGS. 1B and 1D,the diameter D₂ is greater than D₁ and L₂ is less than L₁ because thespring has expanded, becoming less tightly wound and having fewer coils14. The alternate, double spring embodiment resiliently expands from itsrestrained first configuration to its larger profile, secondconfiguration more gradually than does the single spring implant 10. Thecounter rotation of the oppositely wound spring segments 28 serves toslow the unwinding of the device, thereby providing control over themagnitude of injury experienced by the surrounding tissue.

The implant is more easily delivered into the intended tissue locationwhile in the first configuration of FIGS. 1A and 1C. The reduced profilepresented by the spring in a smaller diameter D₁, on the order of1.0-1.5 mm, can more easily penetrate tissue. A channel need not bepreformed by removing tissue through coring or laser techniques to placethe implants. The implants are not intended to maintain a patent channelthrough the subject tissue through which blood can flow. The implants ofthe present invention induce angiogenesis by interacting with the tissueand blood already in the area into which they are placed. Once implantedin the tissue, the expansion of the implant to its larger profile,second configuration, on the order of 2.0-2.5 mm, serves not only tohelp anchor the implant within the tissue, but also serves to irritateand injure the surrounding tissue into which it is implanted.Preferably, the spring embodiments are fabricated to have an unstressedconfiguration equivalent to the second configuration shown in FIGS. 1Band 1D as this will be the final implanted configuration of the deviceafter release from its delivery device. The expanding implants mayrupture and push aside tissue, which permits the inflow and collectionof blood from the surrounding area. However, maintaining a patentchannel for blood flow through the implant is not necessary.

A more important aspect of the presence of the implants is that injuryresponse exhibited by the surrounding ischemic tissue is maximized andangiogenesis is initiated by the resulting thrombosis and fibrin growthas described above. The implants remain expanded against the surroundingtissue after implantation becoming clotted with thrombosis and fibringrowth throughout the implant structure. After the new tissue hassurrounded and ingrown the implant new vessel growth will emerge in theregion to supply the new tissue. At this advanced stage of injuryresponse and healing, the stress applied on surrounding tissue by theexpanded implant may be minimal or nonexistent because tissue has grownaround and accommodated the implant.

Access to ischemic tissue sites within a patient to deliver the implantsof the present invention may be accomplished percutaneously, surgicallyby a cut-down method or thoracically. However, the less invasive andtraumatic percutaneous approach of delivering the implants is generallypreferred. A percutaneous delivery device for delivering the implants tothe myocardium of the heart is shown in FIGS. 2A-2C. FIG. 3 shows adiagrammatic sectional view of the left ventricle 2 of a human heart 1into which the delivery device gains access. Each of the implantembodiments described herein may be delivered percutaneously through adelivery catheter 36, shown in FIGS. 4A-4D, as will be described indetail below. It is noted that, throughout the description of theimplant embodiments and their associated delivery systems, “proximal”refers to the direction along the delivery pathway leading external tothe patient and “distal” refers to the direction along the deliverypathway internal of the patient.

To reach the left ventricle of the heart percutaneously, a guidecatheter (not shown) is first navigated through the patient's vessels toreach the left ventricle 2 of the heart 1. A barb tipped guidewire 34may then be inserted through the guide catheter and into the ventriclewhere it pierces the myocardium 4 and becomes anchored within thetissue. After anchoring the guidewire, the guide catheter is withdrawn,and a steerable implant delivery catheter 36 may be advanced over theguidewire to become positioned within the ventricle for delivery of theimplants. To facilitate delivery of multiple implants, the guidewirelumen of the delivery catheter 36 may be eccentrically located on thecatheter 36. Therefore, when the catheter is rotated about theguidewire, the center of the catheter will rotate through a circularpath as demonstrated in FIGS. 4C and 4D, to encompass a broader deliveryarea with one guidewire placement. The outside diameter of the deliverycatheter is preferably less than 0.100 inch. Additionally, as shown inFIG. 4E, the delivery catheter 36 (implant and push tube not shown) maybe provided with steering capability by means of a pull wire 35extending the length of the catheter in pull wire lumen 37 and attachedby a bond 39 at its distal end. Pulling on the wire 35 from the proximalend causes the more flexible distal tip of the catheter 36 to bedeflected, thereby providing steering control. Steering capability thusprovides a broader range of delivery area with a single catheterization.

FIGS. 2A and 2B show the delivery of the spring implant 10 into tissue.The implant may be carried to the delivery location over a flexible pushtube 20 that is slidable through the steerable delivery catheter 36.FIG. 2C shows the alternate embodiment of the spring implant 26 mountedon the push tube 20. The push tube over which the spring implants arecarried may be an elongate flexible hypodermic tube and be configured tohave a sharp distal end 22 for piercing the surface of tissue into whichthe implant will be placed. Additionally, the push tube slidablyreceives a release wire 21, which extends through thread loops 24 thatpass through side holes 25 at the distal end of the push tube 20 andwrap around tabs 18 of the spring. In the case of the alternateembodiment, a thread loop 24 extends from the release wire, through aside hole to capture the bridge 29 as well. By the interlocking of thethread loops with the release wire within the push tube, the ends 16 ofthe spring are held close to the push tube 20 to maintain a tightlywrapped diameter, extended length, first configuration during deliveryof the device into the tissue. The tabs 18 preferably have a bulbousconfiguration of greater diameter than the filament 12 to prevent thetabs from slipping through the thread loop.

After being advanced through the delivery catheter 36 which has beenplaced adjacent tissue to be treated, the push wire 20 is advanceddistally, independently of the delivery catheter 36, so that the sharpdistal tip 22 pierces the tissue, as shown in FIG. 2A. Continued furtherdistal movement of the push wire 20 advances the implant into the tissuewhere it can be released to assume its second configuration having agreater profile than the first configuration. The depth to which theimplant is placed within the tissue is not believed to be a significantfactor in the ultimate success of the device, however, placement withinthe tissue within an area believed to have the most significant amountof vascular activity is desirable. For example in the case of myocardialtissue, it has been observed that areas closer to the endocardialsurface are generally more active to create pumping action in themyocardium than are areas closer to the epicardial surface. Therefore,when placing implants in myocardial tissue, placement near theendocardial surface is preferred, though it is not necessary to placethe implant flush with the surface. It is understood that an area ofactive, moving muscle tissue will cause the implants of the presentinvention to flex, at least slightly with the surrounding tissue duringthe cardiac cycle.

Once the implant is located within the tissue, release wire 21 iswithdrawn proximally relative to the push tube 20. Thread loops becomereleased from the wire 21 and are free to pass through side holes 25 asthe spring resiliently expands to its second, large profileconfiguration, within the tissue. The greater profile and increaseddiameter of the implant in the second configuration puts an immediatestress on the surrounding tissue causing some tearing. After expansionto the second configuration, the surrounding tissue 4 may tend toherniate into the implant device at herniation points 28 located betweenthe coils 14 of the implant. After implantation, the push tube 20 iswithdrawn proximally through the interior 15 of the implant and backinto the delivery catheter 36 together with the release wire, and theassembly withdrawn from the patient. The thread loops 24, preferablyabsorbable suture material, may be left behind, attached to the implant.

In the case of implants placed within myocardial tissue 4 of the heart1, several implants 8 may be placed within a region of ischemic tissueas shown in FIG. 3. The implants 8 generally expand to a diameter ofapproximately 2 mm and are preferably spaced so that each implant servesan area of one square centimeter. Though any number of implants may beplaced, the density of approximately one per square centimeter ispreferred so as not to interfere with the muscular function of thetissue to which they are implanted. In other words, many implants withina certain area could potentially interfere with the motion of the muscletissue to the detriment of other necessary functions of that tissue.Multiple implants are delivered to a given tissue location by repeatingthe steps recited for delivering a single implant.

In addition to inducing an injury response by expanding within thetissue, the implants induce angiogenesis within the surrounding tissue 4by other mechanisms. One such mechanism is a process of thrombosis ofthe blood surrounding an implanted device 10 and being permitted to poolwithin the interior 15 of the device. Blood that pools around theimplant or in the implant thrombosis which leads to fibrin growth andnucleation of arterioles that become vessels to supply blood to thehealed region. This process may be further enhanced by application of anangiogenic substance to the implant device. The substance may be a solidor fluid placed within the interior 15 of the device before or afterdelivery of the implant so that it comes into contact with and isdistributed by blood entering and surrounding the implant. To deliverthe angiogenic substance to the implant after it has been delivered intotissue, the delivery device may be configured as a conduit through whichthe substance can be transmitted and released into the implant while thedelivery device and implant are still associated. In the case of thetubes and catheters discussed above in connection with a percutaneousdelivery technique, the angiogenic substance may be advanced from theproximal end of the tube, outside the patient, through the lumen of thetube and expelled from a port at the distal end of the tube and into oraround the implanted device. Alternatively, the angiogenic substance maybe coated onto the device or the device may be made from such asubstance.

Another embodiment of the vascular inducing implants is shown in FIG.5A. A mesh tube implant 40 is shown in its low profile firstconfiguration, suitable for delivery into tissue. The mesh tube iscomprised of a mesh pattern of wire like elements 42 that are formedfrom a material that is flexible yet sufficiently rigid to maintain anexpanded, second configuration having a larger profile than its firstconfiguration. The mesh tube embodiment may be fabricated from a thinmetal sheet etched out a pattern of spaces or openings and then rolledand the ends joined to form a tube. Alternatively, the implant may beformed from a fabric such as dacron rolled into a tubular shape. In apreferred embodiment, the braided tube is formed from wire elements 42woven together to form a tube with the elements slidable relative toeach other. The mesh may be resiliently expandable, remaining expandedby the inherent resilience of the material selected, such as highlyelastic or high tensile strength material. Alternatively the mesh tubemay be plastically deformed to its second configuration, if the elementsare formed from a malleable alloy.

In the wire mesh tube embodiment, the wire ends 46 are joined to rings44. As shown in FIG. 5C the ends 46 of the wire elements 42 may bejoined to the end ring 44 at connections 48. The rings 44 may be polymertubes heat shrunk to the element ends to form the connections.Alternatively, the rings may be stainless steel, connected to theelements by solder joints. The elements may be fabricated to be movablerelative to the ring 44. Although not shown, the ends 46 of the elementsmay be formed to have eyelets that are threaded around a narrow end ring44. Thus, the elements would be free to adjust their position along thering during expansion from the first to the second configuration.Additionally, as shown in FIG. 5C, the ring 44 may be non-continuous,having a split 50 across its surface to promote expandability. In thisconfiguration, the ring 44 may provide the supporting force to keep theimplant in its expanded second configuration. The split 50 in the ring44 permits the ring to be coiled into a small configuration fordelivery, yet expand and uncoil into a larger configuration.

The ring 44 may be resiliently expandable, whereby its natural tendencyis to have an uncoiled configuration and maximum diameter. In thisembodiment, the ring is confined in a coiled smaller diameter duringdelivery to the intended tissue location and is released to uncoil andresiliently expand to its larger configuration once placed in thetissue. The elements 42 join to the rings 44 at both ends of the meshtube embodiment thus slide into the second, larger profile configurationunder the force of the resilient rings 44. Alternatively, the rings 44may be plastically deformable so that they expand along with themovement of the elements 42 of the mesh tube 40 as the length of thetube is compressed to cause radial expansion.

The mesh tube implant may be delivered over a delivery system comprisinga relatively stiff small diameter tube 52, such as a hypotube havingslidable within its central lumen a piercing release wire 54 as shown inFIGS. 6A and 6B. In FIG. 6A the mesh tube 40 is supported fromlongitudinal movement at its proximal end 56 by a stop 60 mounted on theexterior of the hypotube 52. The distal end 58 of the mesh tube issupported from longitudinal movement by a small catch member 62 mountedon the exterior of the release wire 54. Both the catch 62 and the stop60 engage the rings 44 at the proximal and distal ends of the mesh tube40. The hypotube 52 and release wire 54 carrying the mesh tube 40 aredelivered to the intended tissue location through a previously placedsteerable catheter 36 as was described in connection with FIGS. 2A and2B. The steerable delivery catheter 36 is not shown in FIGS. 6A and 6Bbut is understood to be part of the delivery system. While tension isapplied on the mesh tube by placing slight pressure on the release wire54 in the distal direction and maintaining pressure on the hypotube 52in the proximal direction, the mesh tube is maintained in its lowprofile extended length first configuration. The combination is togethermoved distally toward the intended tissue location.

In the case of implantation in the myocardium, the sharp piercing distaltip 64 of the release wire 54 penetrates the endocardial surface 6 toprovide access to the myocardium 4. After placement of the mesh tubewithin the myocardium 4, it is expanded to its second configuration bymoving the hypotube, which engages the proximal end 56 of the tube, in aproximal direction while moving the catch 62 on the release wire 54 in aproximal direction. Thus the ends 58 and 56 of the mesh tube are movedcloser, thereby shortening the length of the tube and causing it toexpand radially, placing stress on the surrounding myocardial tissue 4.After expansion of the mesh tube, the release wire 54 may be withdrawnproximally so that its piercing distal tip 64 is within the hypotube 52.The combination can then be withdrawn from the patient without risk ofinjury to vessels from the sharp tip during withdrawal.

FIGS. 7A and 7B show yet another embodiment of the vascular inducingimplant comprising a resiliently expandable rolled tube 70. The rolledtube may be fabricated from a flat sheet 72, as shown in FIGS. 8A and8B. The material is preferably flexible, but will maintain a resilientenergy after being bent into a tubular shape tending to maintain thetube in a relatively expanded, large diameter configuration. A metalsuch as stainless steel or a high density polymer is a preferredmaterial. The tube material may be a solid or may be porous such as amesh screen. The flat sheet is preferably configured to have formedalong one longitudinal edge 76 a tubular ridge 78 that will serve as alock for holding the sheet in a tubular configuration while beingdelivered to the tissue location, as will be described in further detailbelow. The tubular ridge 78 may be a separate tubular segment that isattached to the flat sheet 72 by bonding such as adhesive, soldering orwelding. Alternatively the tubular ridge may be formed by curving over alongitudinal edge 72 of the sheet to define a tube along that edge.

Placing the flat sheet into the low profile first configuration requiresrolling the flat sheet 72 into a tightly wound roll to define thecylindrical structure of the tubular implant 70. In this firstconfiguration, the rolled tube may be coiled upon itself several timesto form a small outer diameter D₁ as shown in FIG. 7A. Force is requiredto maintain the rolled tube implant in the first configuration becausethe elastically deformed sheet material 72 naturally tends to the largerdiameter D₂ of the second configuration shown in FIG. 7B. The rolledtube is implanted in the tissue in the first configuration shown in FIG.7A and permitted to expand to its equilibrium configuration representedin FIG. 7B having a larger profile (diameter) than the firstconfiguration.

As with the other embodiments, the expansion of the rolled tube withinthe subject tissue creates slight injury to the tissue surrounding theimplant as well as provides a device for interacting with blood from thesurrounding tissue to initiate the process of angiogenesis as wasdescribed above. In the case of a rolled-tube formed from a porous ormesh material, further injury to the tissue which surrounds the implantis expected due to the rough surface of the implant material andconstant dynamic contact with the tissue. Additionally, the porous ormesh material may enhance fibrin growth through the device to furtherenhance angiogenesis.

Delivery of the rolled tube embodiment 70 is shown in FIGS. 9A and 9B.As with the other implant embodiments of the present invention, therolled tube embodiment may be delivered to the subject tissuepercutaneously, thoracically or surgically by a cut-down method. Indelivering the implant to myocardial tissue of the heart, percutaneousdelivery is preferred because it is least invasive and traumatic to thepatient. FIGS. 9A-9D depict delivery of the rolled tube implantpercutaneously to the myocardial tissue 4 of the heart. After the leftventricle 2 has been accessed by a steerable delivery catheter 36 asdescribed above, the delivery catheter is anchored in position adjacentthe intended tissue location by a barbed tip guidewire 34 that extendsthrough an eccentric guidewire lumen 32 of the delivery catheter. Thebarbed tip guidewire is anchored in the myocardial tissue 4. The rolledtube 70 is carried through the central lumen 38 of the delivery catheter36 over a coaxial arrangement of a push tube 80 and piercing wire 82having a piercing distal tip 84. The piercing wire 82 is longitudinallyslidable with respect to the push tube 80 so that it may be extendedrelative to the push tube to release the rolled tube as will bedescribed below.

The push wire has formed along its length a backstop 86 configured as adisk radially extending from the push tube to provide surface againstwhich the proximal end 88 of the rolled tube can abut during delivery.To restrain the rolled tube in its first configuration during delivery,the backstop may additionally have two longitudinally and distallyextending protrusions 90 and 92. The inner protrusion 90 extendingwithin the interior of the tubular ridge 78, which is arranged to be atthe edge of the outermost coil 93 of the rolled tube during delivery.The outer protrusion 92 holds the outermost coil 93 from its outersurface, working in conjunction with the inner protrusion to maintainthe tube in its small diameter first configuration against the resilientexpansive force inherent in the rolled tube. The distal end 94 of therolled tube is supported in its compact first configuration by aproximally and longitudinally extending protrusion 96 which resides inthe interior 79 of the tubular ridge 78 at the distal end 94 of therolled tube. The protrusion 96 extends proximally from the sharpeneddistal end 84 of the piercing wire 82.

With the rolled tube located between the protrusions 90, 92 at theproximal end 88 and piercing wire 82 extending through its interior 74.With the sharpened distal end 84 protruding from the distal end 94 ofthe rolled tube to pierce the tissue into which it is to be delivered.The protrusion 96 extends proximally, back into the interior 74 of thetube. In this configuration, the push tube, piercing wire and rolledtube combination is advanced, together, distally out of the distal endof the delivery catheter 36 as shown in FIG. 9B so that the piercingdistal tip 84 of the piercing wire penetrates the surface of the tissue6. The assembly is advanced distally into the tissue 4 to a depth thatreceives the entire implant as shown in FIG. 9D. The proximal end 88 ofthe implant may, but need not be flush with the surface 6 of the tissue4.

After the tube is delivered into the tissue, the piercing wire 82 ismoved distally and the push tube 80 is moved proximally, in oppositedirections relative to each other, so that the backstop 86 andprotrusions 90, 92 and 96 move away from the ends of the tube, releasingit from the confined, first configuration so that it expands to itssecond, larger profile configuration shown in FIGS. 9C and 9D. After thetube is released from the push tube and piercing wire, the piercing wireis withdrawn proximally through the interior 74 of the now expandedrolled tube 70 into the push tube 80, which is then withdrawn into thedelivery catheter 36. The barbed tip guidewire 34 is then pulled fromits anchored location within the tissue 4 and the entire deliverycatheter 36 is withdrawn from the patient.

FIG. 10A shows another embodiment of the vascular inducing implants. Aspine implant 100 is comprised of a plurality of expandable c-shapedrings 102 concentrically arranged along an axial support or spine 104.Each ring is joined to the spine at a point along their circumference.The spine is tangent to each ring 102, with each ring lying in a planethat is normal to the axis of the spine. A discontinuity 106 at the topof each ring permits the rings to expand between two configurations: afirst, low profile configuration in which the ends 108 of the ringoverlap to define a ring of relatively small diameter and a secondconfiguration that presents a larger profile, in which the leaves of thering are open and do not overlap defining a larger diameter and profile.

The spine implant embodiment may be a unitary structure formed from anelastically deformable material such as a plastic or stainless steel.Alternatively, the rings 102 may be separate components that areadjoined to the spine by welding, soldering or bonding. The ends of eachring are preferably formed to have eyelets 110. By locking the eyelets110 together, the resiliently expandable rings 102 may be maintained ina reduced profile, closed configuration, against the inherent expansiveforce. An elongate release pin 112, shown in phantom in FIG. 10A, may beinserted through the aligned eyelet pairs of all the closed rings on thespine. The pull pin 112 may be inserted through the eyelets to maintainthe rings 102 in a closed configuration by maintaining each ring 102 ina closed configuration, with the eyelets 110 aligned concentrically. Therings 102 may be expanded after implantation within the tissue bypulling the pin from the eyelets to release the rings and permitresilient expansion as will be described in further detail below.

FIGS. 11A-11D illustrate the delivery of the spine implant 100. FIGS.11A and 11B show the implant in its first, low profile configuration,which is maintained during deliver and insertion into the intendedtissue location. As with the other embodiments described above, theimplantation of the device will be described as it is implanted intomyocardial tissue of the heart. Although the device may be delivered bya variety of methods including surgically or thoracically, the preferredmethod of delivery is percutaneous, accessing the myocardium 4 throughthe left ventricle of the heart as is shown in FIGS. 4A-4D.

The spine implant 100 is delivered over a push wire 114 that is slidablethrough the delivery catheter 36. The push wire extends through thecenter of the rings during delivery while they are in their closed,small profile configuration. The push wire 114 may be of a diameterwhich is approximately the same size as the inside diameter of the ringsin their closed, small profile configuration to remove any slack betweenthe implant and the push wire during delivery. The pull pin 112 extendsthrough the eyelets 110 and is parallel with the push wire 114 throughthe delivery catheter 36 where it can be manipulated independently ofthe push wire at its proximal end extending outside the patient.

The push wire 114 has a sharpened distal end 118 that is capable ofpiercing the tissue surface 6 to provide an entry site into which theimplant may be inserted into the tissue 4. To prevent proximal movementof the implant on the push wire during delivery into the tissue 4,either the pull pin 112 or the push wire 114 may have formed on itssurface a backstop against which the most proximal ring 102 can abut toresist distal movement. After insertion of the implant into the tissue,the pull pin 112 may be pulled proximally to be removed from the eyeletsof the rings 110 permitting them to resiliently expand to the openconfiguration as shown in FIGS. 11C and 11D. After the pull pin has beenwithdrawn to expand the implant to its second, larger profileconfiguration, the push wire 114 may be withdrawn proximally through thecenter of the rings and out of the tissue and the delivery devicewithdrawn from the patient.

FIGS. 12A-12D show another embodiment of the implant device having afirst configuration that is uniaxial and a second configuration in whicha portion of the device becomes biaxial or bifurcated. The bifurcatedimplant 120 is preferably a hollow unitary structure essentiallycomprised of three tubular sections arranged similar to a pair of pants.Specifically, the implant has a trunk portion 122 having a generallytubular configuration which splits into a first leg 124 and a second leg126, each about one-half the diameter of the trunk portion and having alength that is approximately one-half the length of the entire implant.As shown in FIGS. 12A and 12B, the legs 124 and 126 are closed, theirlongitudinal axes lying parallel to the central axis of the trunkportion 122. In this first configuration, the implant 120 presents a lowprofile suitable for penetration and delivery into tissue.

FIGS. 12C and 12D show the implant in its second, large profileconfiguration wherein the legs 124 and 126 are split apart; curved awayfrom each other such that their axes approach an angle of 90° relativeto the central axis of the trunk portion 122. When moved to the secondconfiguration, the split legs of the implant serve to stress and injuresurrounding tissue into which the implant has been inserted. The tearingand abrasion of the tissue surrounding the now expanded legs 124 and 126respond to the injury through a healing process that leads toangiogenesis as described above. Additionally, because the legs stay intheir expanded configuration, the tissue continues to be irritated bythe presence of the implant, thereby continuing the injury response andinitiation of angiogenesis.

FIG. 13 shows a variation of the biaxial implant 120 having a slantedprofile edge 130 formed along the ends of the legs 124 and 126 to helpto facilitate penetration through the tissue. Although the blunt edgetubular ends of the legs 124 and 126 as shown in FIGS. 12A-12D may besuitable for penetrating soft tissue, the angled edge 130 shown in FIG.13 provides a sharper profile to pierce tough layers of tissue. Theangled edge may be configured in many ways other than the sloping edgeshown in FIG. 13. For example, the second leg 126 may have an edge thatis angled in the reverse direction from the edge of leg 124 to form anarrowhead profile (not shown).

The biaxial implant may move from its first, compact profileconfiguration to its second, expanded profile configuration either byinherent resiliency of the implant material, or by a plasticdeformation. To expand the plastically deformable embodiment, asplitting force may be applied between the legs of the implant once ithas been inserted into tissue. The splitting force may be applied by apull wire extending through the interior of the implant, having a largeprofile distal tip that runs between the adjoining legs as the pull wireis moved in a proximal direction and removed from the center of theimplant through the trunk portion. Alternatively, and in a preferredmethod, the implant is resiliently expandable and may be delivered andexpanded to the extended tissue location over two guidewires as isdescribed in detail below.

FIGS. 14A and 14B illustrate the delivery of the bifurcated implantembodiment into tissue such as myocardial tissue 4 of the myocardium. Aswas described with relation to the other embodiments, the bifurcatedembodiment is preferably delivered percutaneously to the myocardiumthrough a steerable delivery catheter 36 that has been inserted into theleft ventricle of the heart adjacent the myocardial tissue to receivethe implant. The bifurcated implant 120 is carried through the deliverycatheter 36 over a guide tube 132 sized to fit closely the insidediameter of the trunk portion 122 of the implant. Through the guide tube132 extends two support wires 134 and 136 that extend through the trunkportion of the implant and into the legs 124 and 126 during delivery.The support wires 134, 136 are relatively stiff to maintain the legs124, 126 in their joined, low profile first configuration as shown inFIG. 14A. The wires and guide tube are slidable relative to each otherand through the delivery catheter 36. During delivery, the guide tubeextends into the interior of the implant only through the trunk portion122. The support wires 134, 136 extend distally beyond the trunk portionand into each leg to act as stiffening members, providing axial supportfrom the inside diameter of each leg to resist the resilient force ofthe legs to bend apart from each other.

During delivery, the entire assembly is moved distally, with the guidetube 132 and wires 134, 136 being pushed distally to expose the implantfrom the distal end of the delivery catheter 36 so that it may penetratethe endocardial surface 6 and enter the myocardium 4 as shown in FIG.14B. The delivery force pushing the implant in the distal direction isapplied by the distal end of the guide tube 132 engaging the junction ofthe legs 138. After the implant has been inserted into the tissue 4, thesupport wires 134 and 136 are withdrawn proximally from the legs 124,126 of the implant permitting them to expand apart from each other toinjure the surrounding tissue and place it in a stressed condition thatwill be maintained by the implant in its second configuration. Inaddition to providing a constant source of irritation and injury to thetissue, the expanded implant serves to resist migration out of thetissue despite tissue movement because the implant has clawed into thetissue during expansion. After deployment of the implant the guide tube132 and support wires 134, 136 are withdrawn further proximally, intothe delivery catheter 36, which then may be withdrawn from the patient.

Another embodiment of a bifurcated implant is shown in FIGS. 15A-15D.The open spring bifurcated implant 140 is intended to have a trunkportion 142 and two leg portions 144 and 146 similar to the bifurcatedembodiment discussed above. The open spring bifurcated embodiment maycomprise two helically wrapped coil springs 148, 150 joined togetheronly at the proximal end 152 of the trunk portion. Alternatively, thebifurcated spring embodiment may comprise a single spring that is woundto double back upon itself at the proximal trunk coil 152 and definingtwo legs 144 and 146 extending therefrom that are defined by each end ofa single spring. The coil spring should be flexible and capable ofmaintaining substantially its expanded bifurcated and larger profileconfiguration under the collapsing force of the stressed tissue in whichit is implanted.

The first, low profile configuration of the implant is shown in FIGS.15A and 15C. The coils 152 of each of the legs 144 and 146 interleave sothat they substantially lie along the same longitudinal axis as thetrunk portion 142. In this configuration, the overall profile of theimplant 140 is minimized, facilitating delivery of the implant intotissue. FIGS. 15B and 15D show the implant in its larger profile secondconfiguration. The free ends of each of the legs 144 and 146 springopen, naturally inclined to the Y-shape bifurcated configuration,because they are plastically deformed to have that shape during theirformation. The profile of the implant is increased by the movement ofthe leg portions away from the axis of the trunk portion 142. Whenpermitted to expand within the subject ischemic tissue, the expandingleg portions are expected to cause some minimal injury and possibletearing of the tissue into which it is implanted. The injury, which willbe continually irritated by the presence of the implant in its secondconfiguration, is expected to instigate a healing response by the tissuethat will initiate angiogenesis by the mechanisms described above.

FIGS. 16A and 16D illustrate the steps of delivering the bifurcated openspring implant into ischemic tissue 4. In FIG. 16A, the implant ismaintained in its uniaxial, low profile first configuration by arelatively stiff piercing wire 158 having a sharpened distal tip 160 forpiercing the surface of the tissue 6. The piercing wire 158 extendsthrough the interior 162 of the spring embodiment, retaining the coils154 of the legs 144 and 146 along the central axis by contacting theirinside surfaces. The legs are held against movement by the presence ofthe wire 158. The sharpened tip 160 of the piercing wire protrudes fromthe distal end of the implant so that it will be first to contact thetissue during distal movement to the implant site.

Push tube 156 is slidable over the push wire and has a larger diameterthan the push wire, sized to engage the circumference of the mostproximal coil 152 of the implant. The push tube delivers a pushing forceagainst the implant during insertion into the tissue, when both thepiercing wire 158 and push tube 156 are moved distally in unison tomaintain the piercing wire through the implant which is maintained inits first configuration. Also the push tube 156 can move independentlyof the piercing wire 158, so that once the implant has been delivered toa proper depth within the tissue 4, the piercing wire 158 may beretracted into the push tube as shown in FIG. 16B, to release the coils154 to their expanded second configuration. After delivery and releaseof the implant into the ischemic tissue, the push tube 156 and piercingwire 158 may be retracted proximally into the steerable deliverycatheter 36 and the entire assembly withdrawn from the patient.

FIGS. 17A-17D show a variation of the open spring bifurcated implantembodiment. The bifurcated loop implant 170 is comprised of first andsecond spines 172, 174 each having a plurality of circular loops 176.The loops 176 are joined to the respective spines at a point aroundtheir circumference such that they are arranged substantiallyconcentrically. The spines 174, 172 share several common loops 176 in atrunk portion 178 of the implant. The free ends of the spines 172, 174form leg portions 180, 182 of the implant, respectively. The implant isshown in its first low profile configuration in FIGS. 17A and 17C.

In the first configuration, the loops 176 of both spines and the trunkportion are interleaved and lie substantially along the samelongitudinal axis. In the expanded second configuration, the legportions 180 and 182 spring apart under the resilient force of thespines 172 and 174 which are preformed to have a curved configuration,yielding the large profile configuration shown in FIGS. 17B and 17D. Theimplant is delivered into the subject ischemic tissue 4 by the stepsdiscussed above in connection with the open spring bifurcated embodimentand which are illustrated in FIGS. 18A and 18B. The piercing wire andpush tube 158, 156, respectively, may be used to deliver the loopbifurcated implant 170 in the same manner as the open spring embodimentdescribed above.

Another implant embodiment is shown in FIGS. 19A-19D. A brush implant240 is comprised of a central core member 242 having a plurality ofresilient bristles 244 extending radially therefrom to irritatesurrounding tissue. The bristles 244 of the brush 240 collapse againstthe core 242 during distal movement into the tissue during delivery todefine a low profile fist configuration. After delivery into the tissuethe bristles resiliently expand in a radially outward direction, withrespect to the core, to define a larger profile second configurationthat irritates and places stress on surrounding tissue.

The central core member 242 is preferably somewhat rigid to facilitateinsertion into the tissue 4. The core may be solid or a hollow tube todefine a central lumen 246 over which the implant can be delivered intothe intended tissue location. Additionally, the central lumen 246 maycontain an angiogenic substance to be delivered to the intended tissuelocation along with the implant. Alternatively, the core 242 of thebrush implant may be comprised of several wires helically wrapped aroundeach other along a single axis as shown in FIGS. 19D and 19E. The brushimplant shown in FIG. 19D is comprised of three helically wrapped wires248, 250 and 252 defining the core 242. Wedged in between the wrappedwires are bristles 244 which extend radially from the core 242. As shownin FIG. 19E, the three helically wrapped wires define a central opening254 through the center of the core. The central opening may be usefulfor holding an angiogenic substance or thrombus of blood within theimplant that will later interact with blood flow after implantation.Additionally, the central opening 254 may receive a guidewire so thatthe implant may be delivered to its intended location by tracking overthe guidewire that has been inserted into a patient. Alternatively, thecore 242 may be formed from only two separate wires that are helicallywrapped about each other; however, a central opening 254 may not besubstantially defined by only two wires.

The bristles 244 attached to the core 242 serve injure and irritatesurrounding tissue into which it is implanted to cause an injuryresponse that leads to angiogenesis. The bristles resiliently extendfrom the core in a radially outward direction to place stress onsurrounding tissue and cause irritation. The bristles provide aplurality of contact points with the surrounding tissue where irritationoccurs, providing a plurality of nucleation sites where angiogenesis canbe initiated.

Tubes may be used in place of the wires that form the core 242 and alsothe bristles 244. Tubular bristles and core wires provide lumens thatcan retain a quantity of an angiogenic substance or thrombi of bloodintended to interact with the surrounding tissue into which the deviceis implanted. The core wires may have an outside diameter of 0.008 inchand the bristles may have an outside diameter on the order of 0.006 inchto 0.010 inch. The bristles may be made from stainless steel or plastic.

As with the embodiments described above, the brush implant may bedelivered percutaneously, thoracically or surgically via a cut-downmethod to the intended tissue location. By way of example, FIG. 19Frepresents the brush implant being delivered percutaneously into themyocardium 4. A suitable delivery system for the brush type implant mayinclude a steerable outer catheter 36 within which a slidable smallerdiameter brush carrier catheter 260 having a central lumen 262. Thedistal end 264 of the brush carrier catheter is sharpened to be capableof piercing the endocardial surface of the myocardium 8.

A brush implant 240 is pushed through the central lumen 262 of thecatheter 260 in a distal direction by a push wire 266 that is also sizedto fit within a central lumen of the catheter. Therefore, to deliver abrush implant into tissue, the distal end of the steerable catheter 36is brought in proximity to the intended tissue location as shown inFIGS. 19F and 19G. The brush carrier catheter carrying a brush implant240 and push wire 266 within its central lumen 262 is navigated distallythrough the steerable catheter and out its distal end so that thesharpened distal end 264 of the catheter will pierce the surface of thetissue to permit delivery of the implant. After the distal end of thecatheter has been advanced slightly into the tissue 4, the push wire 266is moved distally to push the brush implant 240 out of the distalopening 268 of the catheter 260.

Alternatively, the distal end of the brush carrier catheter 264 need notbe sharpened to pierce the tissue implant location. Rather, the brushimplant itself may have a sharpened distal tip 270 formed by the wrappedwires or hypotube of the core 242 that is capable of penetrating thetissue 4 with pushing force provided from the push wire 266. Afterimplantation, the push wire 266 and brush carrier catheter 266 may bewithdrawn proximally back into the steerable catheter 36 and the implantsystem 258 withdrawn from the patient. The distal movement through thetissue that occurs during implantation causes the bristles 244 tomaintain an acute angle with a longitudinal axis of the brush implant,pointing in the proximal direction. After the brush is implanted, thebristles tend to resiliently return to a radially outward extendingposition that places stress on the surrounding tissue and causesirritation. Additionally, the bristles act as barbs to prevent proximalmigration of the implant.

From the foregoing it will be appreciated that the invention provides animplant and delivery system for promoting angiogenesis within ischemic,viable tissue. The invention is particularly advantageous in promotingangiogenesis with an ischemic myocardial tissue of the heart. Theimplants are simple and readily insertable into the intended tissuelocation with a minimum of steps. The delivery systems are simple tooperate to implant the devices quickly and safely.

It should be understood, however, that the foregoing description of theinvention is intended to be illustrative thereof and that othermodifications, embodiments and equivalents may be apparent to thoseskilled in the art without departing from its spirit.

1. A delivery device for placing an implant in the myocardium of apatient comprising: a steerable delivery catheter having at least onelumen and a defined length; an elongate shaft slidable through the lumenof the delivery catheter having a proximal end, a sharpened distal endcapable of piercing tissue and a length greater than the length of thedelivery catheter; means at the distal end of the shaft for releasablyretaining the implant in a low profile first configuration andconfigured to release the implant to a large profile secondconfiguration.
 2. A method of percutaneously delivering an implant tomyocardial tissue comprising: providing an implant having a low profilefirst configuration and a large profile second configuration; providinga delivery catheter having proximal and distal ends and at least onelumen defined between the ends; providing an elongate shaft slidablethrough the lumen of the delivery catheter, having a sharp distal endand means for releasably retaining the implant in its firstconfiguration at the distal end of the shaft; inserting the deliverycatheter in the patient and navigating it through the patient's vesselsto the left ventricle and positioning the distal end adjacent myocardialtissue; advancing the shaft, with the implant retained on the distalend, through the lumen of the delivery catheter so that so that thesharp distal end of the shaft and implant protrude from the distal endof the catheter and penetrate the myocardium; positioning the implant tothe desired depth in the myocardium; releasing the implant from thedistal end of the shaft so that it expands to its second configurationin the myocardium; withdrawing the shaft and delivery catheter from thepatient.